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Saturday, February 16, 2008

Embryo free way to make cells 'safe'

Evidence that it should be possible to take skin cells and safely turn them into embryonic like cells to treat a vast range of diseases is published today.

The work takes doctors one step closer to the day that doctors will not need to clone embryos in order to create an unlimited supply of any of a patient's own cells and tissues for novel treatments and transplants, whether to treat diabetes or Parkinson's disease.

Researchers recently showed that adult human and mouse skin cells could be "reprogrammed" to be capable of generating any type of cell in a manner similar to embryonic stem cells, sidestepping many ethical objections to this work.

Now the pioneer of this method, Prof Shinya Yamanaka of Kyoto University, reports today in the journal Science that his team has moved another step closer to understanding how these "induced pluripotent stem cells" or iPS cells might be reprogrammed without causing tumours when they are transplanted into the body, a crucial step if they are used to study disease or developed for human therapies.

Dr Takashi Aoi and his other colleagues reprogrammed adult mouse liver and stomach lining cells into iPS cells by genetically altering the cell by introducing three new genes with a kind of virus, called a retrovirus.

There have been concerns that the retrovirus could trigger cancer, by introducing the new genes in such a way to cause problems to useful stretches of DNA, for instance genes that suppress tumour growth.

The team was able to confirm in iPS cells made from adult cells that the virus did not insert genes this way. Mice implanted with the rejuvenated cells remained tumour-free six months after receiving the new cells.

But he tells the Telegraph that practical uses of the reprogrammed cells are still years away.

"In order to apply this technology to clinics, we still have to study the safety of iPS cells in bigger animals such as monkeys," he says. "It will take years to do this."

"It is very encouraging that the method does not lead to preferential insertion of the retroviruses into tumour suppressor genes," comments Dr Robin Lovell-Badge of the National Institute for Medical Research, London.

"However, even if rare, this may happen occasionally, so some caution is still needed. The insertions could also effect genes required for the iPS cells to form the specific cell types that might be required for cell-based therapies.

"So it would still be better if the reprogramming method could avoid the use of these viruses. This is one reason why it is still desirable to pursue other methods of reprogramming, such as so-called "therapeutic cloning". Once we understand how reprogramming works we can devise the ideal way to achieve it safely."

Prof Yamanka's work is a remarkable advance that prompted Sir Ian Wilmut, who led the team that cloned Dolly the sheep, to tell The Daily Telegraph that he would adopt the new method rather than the nuclear transfer method that his team used to create Dolly.

The Japanese work has now been confirmed in other laboratories. A few days ago, UCLA stem cell scientists led by Kathrin Plath and William Lowry used genetic alteration to turn back the clock on human skin cells and create cells that are nearly identical to human embryonic stem cells, iPS cells.